Human Gene BLNK (ENST00000224337.9) Description and Page Index
  Description: Homo sapiens B cell linker (BLNK), transcript variant 6, non-coding RNA. (from RefSeq NR_047680)
RefSeq Summary (NM_013314): This gene encodes a cytoplasmic linker or adaptor protein that plays a critical role in B cell development. This protein bridges B cell receptor-associated kinase activation with downstream signaling pathways, thereby affecting various biological functions. The phosphorylation of five tyrosine residues is necessary for this protein to nucleate distinct signaling effectors following B cell receptor activation. Mutations in this gene cause hypoglobulinemia and absent B cells, a disease in which the pro- to pre-B-cell transition is developmentally blocked. Deficiency in this protein has also been shown in some cases of pre-B acute lymphoblastic leukemia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2012].
Gencode Transcript: ENST00000224337.9
Gencode Gene: ENSG00000095585.16
Transcript (Including UTRs)
   Position: hg38 chr10:96,191,702-96,271,540 Size: 79,839 Total Exon Count: 17 Strand: -
Coding Region
   Position: hg38 chr10:96,191,973-96,271,398 Size: 79,426 Coding Exon Count: 17 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr10:96,191,702-96,271,540)mRNA (may differ from genome)Protein (456 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGIneXtProtOMIMPubMed
ReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: BLNK_HUMAN
DESCRIPTION: RecName: Full=B-cell linker protein; AltName: Full=B-cell adapter containing a SH2 domain protein; AltName: Full=B-cell adapter containing a Src homology 2 domain protein; AltName: Full=Cytoplasmic adapter protein; AltName: Full=Src homology 2 domain-containing leukocyte protein of 65 kDa; Short=SLP-65;
FUNCTION: Functions as a central linker protein, downstream of the B-cell receptor (BCR), bridging the SYK kinase to a multitude of signaling pathways and regulating biological outcomes of B-cell function and development. Plays a role in the activation of ERK/EPHB2, MAP kinase p38 and JNK. Modulates AP1 activation. Important for the activation of NF-kappa-B and NFAT. Plays an important role in BCR-mediated PLCG1 and PLCG2 activation and Ca(2+) mobilization and is required for trafficking of the BCR to late endosomes. However, does not seem to be required for pre-BCR- mediated activation of MAP kinase and phosphatidyl-inositol 3 (PI3) kinase signaling. May be required for the RAC1-JNK pathway. Plays a critical role in orchestrating the pro-B cell to pre-B cell transition. May play an important role in BCR-induced B-cell apoptosis.
SUBUNIT: Associates with PLCG1, VAV1 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts with VAV3, PLCG2 and GRB2. Interacts through its SH2 domain with CD79A. Interacts (via SH2 domain) with SYK; phosphorylated and activated by SYK. Interacts with SCIMP.
SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=BCR activation results in the translocation to membrane fraction.
TISSUE SPECIFICITY: Expressed in B-cell lineage and fibroblast cell lines (at protein level). Highest levels of expression in the spleen, with lower levels in the liver, kidney, pancreas, small intestines and colon.
PTM: Following BCR activation, phosphorylated on tyrosine residues by SYK and LYN. When phosphorylated, serves as a scaffold to assemble downstream targets of antigen activation, including PLCG1, VAV1, GRB2 and NCK1. Phosphorylation of Tyr-84, Tyr-178 and Tyr-189 facilitates PLCG1 binding. Phosphorylation of Tyr-96 facilitates BTK binding. Phosphorylation of Tyr-72 facilitates VAV1 and NCK1 binding. Phosphorylation is required for both Ca(2+) and MAPK signaling pathways.
DISEASE: Defects in BLNK are the cause of agammaglobulinemia type 4 (AGM4) [MIM:613502]. It is a primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life.
SIMILARITY: Contains 1 SH2 domain.
WEB RESOURCE: Name=BLNKbase; Note=BLNK mutation db; URL="http://bioinf.uta.fi/BLNKbase/";

-  MalaCards Disease Associations
  MalaCards Gene Search: BLNK
Diseases sorted by gene-association score: agammaglobulinemia 4* (1019), agammaglobulinemia, non-bruton type* (143), b cell linker protein deficiency (17), agammaglobulinemia (11), congenital hypogammaglobulinemia (8), lymphoblastic leukemia (4)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 85.34 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 274.11 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -31.80142-0.224 Picture PostScript Text
3' UTR -55.10271-0.203 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000980 - SH2

Pfam Domains:
PF00017 - SH2 domain

ModBase Predicted Comparative 3D Structure on Q8WV28
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005068 transmembrane receptor protein tyrosine kinase adaptor activity
GO:0005070 SH3/SH2 adaptor activity
GO:0005515 protein binding

Biological Process:
GO:0006954 inflammatory response
GO:0006959 humoral immune response
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway
GO:0009967 positive regulation of signal transduction
GO:0030183 B cell differentiation
GO:0035556 intracellular signal transduction
GO:0042113 B cell activation

Cellular Component:
GO:0005622 intracellular
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0036464 cytoplasmic ribonucleoprotein granule


-  Descriptions from all associated GenBank mRNAs
  AK225546 - Homo sapiens mRNA for B-cell linker variant, clone: KDN02487.
BC018906 - Homo sapiens B-cell linker, mRNA (cDNA clone MGC:10542 IMAGE:4053894), complete cds.
BC110298 - Homo sapiens B-cell linker, mRNA (cDNA clone IMAGE:5213221).
AF068180 - Homo sapiens B cell linker protein BLNK mRNA, alternatively spliced, complete cds.
AF068181 - Homo sapiens B cell linker protein BLNK-s mRNA, alternatively spliced, complete cds.
AK027779 - Homo sapiens cDNA FLJ14873 fis, clone PLACE1002685, highly similar to B-cell linker protein.
KJ898723 - Synthetic construct Homo sapiens clone ccsbBroadEn_08117 BLNK gene, encodes complete protein.
AM180327 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 5-8 and 16 variant.
AM180328 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 6-17 variant.
AM180329 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 5-17 variant.
AM180330 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 8-17 variant.
AM180331 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 6-16 variant.
AM180332 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 8-16 variant.
AM180333 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 4-5 variant.
AM180334 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 5-6 variant.
AM180335 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 4-6 variant.
AM180336 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 16 variant with intron 15 and 16 insertion.
AM180337 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 16 variant.
AM180338 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), variant with splice site slippage and 5-bp intronic insertion between exons 3 and 4.
AM180339 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 6 variant.
AM180340 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 8-9 and 16 variant.
AM180341 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 3,7 and 16 variant.
AM180342 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 3 and 16 variant.
AM180343 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 3 variant.
AM180344 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 3-4 variant.
AM180345 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), delta 3,8 and 9 variant.
AM180346 - Homo sapiens partial mRNA for B-cell linker protein (BLNK gene), variant missing exons 3, and 4 and 5' end of exon 5.
JD305424 - Sequence 286448 from Patent EP1572962.
JD083703 - Sequence 64727 from Patent EP1572962.
JD126519 - Sequence 107543 from Patent EP1572962.
JD445295 - Sequence 426319 from Patent EP1572962.
JD534917 - Sequence 515941 from Patent EP1572962.
JD155968 - Sequence 136992 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04662 - B cell receptor signaling pathway
hsa05340 - Primary immunodeficiency

Reactome (by CSHL, EBI, and GO)

Protein Q8WV28 (Reactome details) participates in the following event(s):

R-HSA-912724 CBL binds B-cell linker protein
R-HSA-983703 p-6Y-SYK phosphorylates BLNK (SLP65)
R-HSA-1112666 BLNK (SLP-65) Signalosome hydrolyzes phosphatidyinositol bisphosphate forming diacylglycerol and inositol-1,4,5-trisphosphate
R-HSA-912631 Regulation of signaling by CBL
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
R-HSA-512988 Interleukin-3, 5 and GM-CSF signaling
R-HSA-983705 Signaling by the B Cell Receptor (BCR)
R-HSA-449147 Signaling by Interleukins
R-HSA-1280218 Adaptive Immune System
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: BASH, BLNK_HUMAN, NR_047680, O75498, O75499, Q8WV28, SLP65, uc001kls.1, uc001kls.2, uc001kls.3, uc001kls.4, uc001kls.5
UCSC ID: uc001kls.5
RefSeq Accession: NM_013314
Protein: Q8WV28 (aka BLNK_HUMAN)
CCDS: CCDS7446.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.